Conventional Treatment In Patients Research Articles

Effects of different modalities of inspiratory muscle training as an add-on to conventional treatment of patients with chronic obstructive pulmonary disease (COPD): study protocol for a randomized controlled trial

BackgroundChronic obstructive pulmonary disease (COPD) leads to peripheral and respiratory muscle dysfunctions. Nowadays, inspiratory muscle training can be geared toward strength or endurance gains. This study aims to investigate the effects of an inspiratory muscle training (IMT) protocol using different therapeutic modalities to be implemented in pulmonary rehabilitation programs. The effects of IMT on exercise capacity were considered as the primary endpoint, and the effects of IMT on inspiratory muscle function, health-related quality of life, and daily physical activity level were considered as the secondary outcomes.MethodsThis study is a blinded-investigator randomized controlled clinical trial. Sixty subjects will be randomly allocated into three groups: (1) pulmonary rehabilitation (PR) associated with inspiratory muscle training without any load (PRWIMT), (2) PR associated with inspiratory muscle training with a linear load (PRIMTLL), and (3) PR associated with inspiratory muscle training with isocapnic voluntary hyperpnea (PRIMTIVH). The protocol will be performed 5 days a week (3 days with supervision) for 10 weeks. The study will assess anthropometric data, lung function, respiratory muscle strength, and functional capacity by the Incremental Shuttle Walking Test and the Six-Minute Walk Test, lung volumes during the submaximal endurance test, peripheral muscle strength of the upper and lower limbs, dyspnea, and quality of life related to health, before and after the training protocol. Normality will be tested using the Kolmogorov-Smirnov test, and variables will be compared by two-way analysis of variance. The significance level was set at p < 0.05. Ethics approval was obtained from the Institutional Ethics Committee in Research (1.663.411). The study results will be disseminated through presentation at specific scientific conferences and publication in peer-reviewed journals.DiscussionThe different IMT protocols used in our study will be able to guide respiratory therapists to understand and to include in conventional PR programs the most effective respiratory muscle training type in subjects with COPD.Trial registrationBrazilian Clinical Trials Registry, RBR-94v6kd. Registered on 11 March 2017.

A prospective study of N-acetylcysteine treatment in drug-induced fulminant hepatic failure

Background: Acute liver failure (ALF) is a rare but severe, life-threatening, complex, multisystemic gastroenterological emergency. Its rapid progression and high mortality demand early diagnosis and expert management. Drug-induced ALF (DI-ALF) remains the uncommon cause of ALF in India. To date, there is no established treatment for DI-ALF other than liver transplantation and little is known about the use of N-acetylcysteine (NAC) in DI-ALF. A prospective case-control study was carried with the aim to determine the effect of NAC on mortality of DI-FHF patients and also to evaluate the safety and efficacy of NAC use.Methods: A total of 18 patients with a diagnosis of DI-FHF were included in the study. 10 patients received NAC infusion for 72 hours whereas the control group received placebo. The variables evaluated were demographic, signs and symptoms, biochemical parameters, outcome and length of hospital stay.Results: Out of 18 DI-FHF patients, 13 (72.2%) had anti-tuberculosis therapy (ATT) induced FHF and 5 (27.8%) patients had ayurvedic induced FHF. The two groups were comparable for the various baseline characteristics (age, INR, alanine aminotransferase, creatinine, albumin, grade of encephalopathy, etc.). The mortality decreased to 20% with the use of NAC versus 75% in the control group (P=0.023). Use of NAC was associated with a shorter length of hospital stay of survived patients (P=0.043). Moreover, the overall survival was improved by NAC (P=0.023) in DI-FHF. ATT induced FHF showed better outcome as compared to ayurvedic induced FHF use (P=0.019).Conclusions: Author recommended the use of NAC along with conventional treatments in patients with DI-FHF in non-transplant centers while awaiting referrals. ATT induced FHF showed better outcome as compared to ayurvedic induced FHF with NAC administration and its use was safe.

Effectiveness and safety of a mixture of diosmin, coumarin and arbutin (Linfadren®) in addition to conventional treatment in the management of patients with post-trauma/surgery persistent hand edema: a randomized controlled trial

Objective: To evaluate the effectiveness and safety of oral administration of Linfadren® in addition to conventional treatment in patients with post-trauma/surgery persistent hand edema. Design: Parallel-group randomized controlled trial. Setting: Outpatient rehabilitation center. Subjects: A total of 60 outpatients (mean age 48.5 (standard deviation (SD) = 12.3) years) with post-trauma/surgery persistent hand edema. Interventions: Patients were randomized to either receive six-week conventional treatment plus Linfadren® (Study Group) or conventional treatment (Control Group). Main Measures: Primary outcome was hand edema as measured by figure-of-eight method. Secondary outcomes were hand function, patient’s overall perceived treatment effectiveness and rescue medication request. Tolerability of Linfadren® was also evaluated. Assessments were performed at baseline, at the end of treatment and three months after the end of treatment. Results: All patients completed the six-week program and 57 patients (95%) completed the three-month follow-up. At six weeks, the Study Group had significantly greater improvement in hand edema (423.3 (SD = 23.8) mm vs 439.4 (SD = 22.6) mm; P = 0.009) and upper limb function (Quick Disabilities of Arm, Shoulder and Hand questionnaire: 23.6 (SD = 13.6) vs 37.7 (SD = 15.9); P = 0.005) compared to the Control Group. Moreover, the percentage of patients who perceived treatment as effective was significantly higher in the Study Group than in the Control Group both after treatment (70% vs 37%, P = 0.002) and at follow-up (77% vs 30%, P < 0.0001). The rescue medication request was not different between groups. No adverse events were recorded. Conclusion: Linfadren® in addition to conventional treatment was safe and more effective than conventional treatment alone in patients with post-trauma/surgery persistent hand edema.

Long-Term Survival in Patients Responding to Anti-PD-1/PD-L1 Therapy and Disease Outcome upon Treatment Discontinuation.

Anti-PD-(L)1 can provide overall survival (OS) benefits over conventional treatments for patients with many different cancer types. However, the long-term outcome of cancer patients responding to these therapies remains unknown. This study is an exploratory study that aimed to describe the long-term survival of patients responding to anti-PD-(L)1 monotherapy across multiple cancer types.Patients and Methods: Data from patients treated with an anti-PD-(L)1 monotherapy in a phase I trial at Gustave Roussy were retrospectively analyzed over a period of 5 years. All cancer types (n = 19) were included. Clinical and biological factors associated with response, long-term survival, and secondary refractory disease were studied. Among 262 eligible patients, the overall objective response rate was 29%. The median progression-free survival of responder patients (RP) at 3 months was 30 months, and the median OS of RP was not reached after a median follow-up of 34 months. In RPs, 3- and 5-year OS percentages were 84% and 64%, respectively. No death occurred in the 21 complete responders (CR) during the overall follow-up. However, many partial responders (PR) showed subsequent tumor relapses to treatment. Long responders (response ≥2 years) represented 11.8% of the overall population. These findings should be validated in further prospective studies. There are currently no differences in therapeutic strategies between CRs and PRs to anti-PD-(L)1. We found a striking difference in OS between these two types of responses. Our results are in favor of evaluating patient stratification strategies and intensification of treatments when tumor lesions of a partial responder to immunotherapy stop improving.See related commentary by Cohen and Flaherty, p. 910.

Clinical and laboratory outcomes of stem cell transplantation in patients with decompensated liver cirrhosis: single-arm pilot trial

Introduction The high prevalence of hepatitis C virus-associated liver disease has led to increasing number of Egyptian patients having end-stage liver disease and requiring liver transplantation. Because of several limitations of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells (MSCs) for liver diseases. Aim The aim of this study was to assess the efficacy of using bone marrow-derived MSC on clinical manifestations, liver function, Child–Pugh score, and Model for End-stage Liver Disease score in patients with decompensated liver cirrhosis. Patients and methods This is a pilot single-arm prospective trial that included 13 patients with hepatitis C virus-associated liver cirrhosis who received transdifferentiated MSC via ultrasound-guided percutaneous portal vein infusion plus regular conventional treatment for patients with cirrhosis. Patients were followed up weekly for the first month and monthly for 6 months. Results There was significant improvement in some clinical manifestations, including frequency of attacks of hematemesis, ascites, and lower limb edema after MSC infusion compared with baseline data. Moreover significant increase was detected in mean serum albumin level as it began with 24.62 ± 3.93 and became 27.81 ± 4.14 (P = 0.009) after 6 months of follow-up. Moreover, the results showed improvement in Child–Pugh, but no changes were detected in Model for End-stage Liver Disease score after MSC infusion compared with baseline. Conclusion Our data show that transdifferentiated MSC injection may improve some clinical manifestations and some indices of liver function in patients with decompensated liver cirrhosis with successful tolerability.

The role of celecoxib for colorectal cancer treatment: a systematic review

Background: Some evidence has suggested that the Cox-2 inhibitor, celecoxib, might improve the survival outcomes in cancer patients. However, the association between celecoxib use and treatment response in colorectal cancer (CRC) patients remains controversial. Thus, a summary on current evidence was performed. Methods: We conducted an electronic search using (PubMed, Web of Science, Embase, and CNKI) to identify relevant peer-reviewed articles, up to March 2018. Eligible study designs included randomized controlled trials (RCTs) and uncontrolled trials (UCTs) with the single experimental arm. The included trials evaluated the effect of adding celecoxib to conventional treatments for patients with CRC on overall response rate (ORR), disease control rate (DCR), pathological response, survival indices, and toxicities. Results: The final analysis included 12 trials with a total of 621 patients. In this study, a qualitative summary and meta-analysis was performed due to insufficient RCTs. The addition of celecoxib showed improvement of pathological response but had no effects on ORR (RR =1.09; 95% CI, 0.62–1.92; P=0.76) and DCR (RR =1.09; 95% CI, 0.94–1.27; P=0.25). The impact of celecoxib on survival indices remains unclear. Meta-analysis on toxicities suggests that celecoxib is well tolerated with a decreased risk of oral mucositis (RR =0.35; 95% CI, 0.18–0.67; P=0.002). Conclusions: Results showed the potential benefits of celecoxib in the treatment of resectable CRC compared with chemotherapy or chemoradiotherapy alone, but there were no effects on ORR/DCR or survival indices. The safety profile was identified in the meta-analysis among CRC patients. The benefit versus harm needs to be carefully considered when celecoxib is recommended in patients with a history of cardiac diseases. In this review, part of the evidence was evaluated from non-RCTs, so further well-designed RCTs in this field are urgently required to confirm our finding.

Biomarkers in colorectal cancer: Current clinical utility and future perspectives.

Colorectal cancer (CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases (75%-80%), but it has been suggested that crosstalk between gene mutations (i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations (i.e., DNA methylation of CpG island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.

Postoperative stress and pain response applying fast-track protocol in patients undergoing hepatectomy

Aim To assess the clinical parameters and compare the stress and pain response between fast-track recovery protocol and conventional treatment in patients undergoing major liver resection. Methods Eighty-eight patients suffering from malignant liver tumours were surgically treated from May 2012 to March 2015. After randomisation, they were prospectively divided into two groups: group fast-track patients (n = 46) and group conventional treatment patients (n = 42). Demographic and clinical data were collected and patients were assessed with pain scale (behavioural observation scale and visual analog scale), while depression levels were evaluated with Zung self-rating depression scale and three Numeric Analog Scale self-reported questions. Peripheral blood samples were collected at time points: T1 on the admission day, T2 on the day of surgery and T3 on the day of discharge examining serum levels of adrenocorticotropic hormone and cortisol. Conclusion Fast-track recovery protocols seem to be associated with improvement in several clinical parameters, without compromising, biologic or emotional stress in patients undergoing major liver resection.

Effectiveness of Intraductal Meibomian Gland Probing in Addition to the Conventional Treatment in Patients with Obstructive Meibomian Gland Dysfunction

ABSTRACTPurpose: To evaluate the effectiveness of intraductal meibomian gland probing in addition to conventional treatment for the management of obstructive meibomian gland dysfunction (O-MGD).Methods: Totally, 40 patients were divided into two groups to receive either conventional treatment alone (group 1: 40 eyes of 20 patients) or conventional treatment plus probing (group 2: 40 eyes of 20 patients). The ocular surface disease index score, Schirmer 1 test, tear film break-up time, Oxford grading of ocular surface, meibum expressibility, and quality scores were evaluated baseline and compared with the end of treatment (day 30 and day 90).Results: There was no significant difference in baseline scores between groups (All p > 0.05). All scores demonstrated significantly improvement from baseline in both group, and it was faster in group 2 (All p < 0.05).Conclusion: This study showed that intraductal meibomian gland probing seems to provide rapid symptom relief and clinical improvement for patients with O-MGD.

STUDY THE EFFICACY OF CHRONIC INTERMITTENT INTRAVENOUS INSULIN INFUSION THERAPY OVER AND ABOVE CONVENTIONAL TREATMENT IN PATIENTS OF DIABETIC AUTONOMIC NEUROPATHY

Objective: This study aims to emphasize the importance of chronic intermittent intravenous insulin infusion therapy (CIIIT) over and above conventional treatment in patients with diabetic autonomic neuropathy.Methods: In our study, we had 50 patients; most of the patients were in the age group of 30–50 years and sex ratio for male:female was 3:2. The patients were divided into two groups. One group which received monthly CIIIT for 8 h per month for 6 months (Group-1) whereas other group did not receive it (Group-2). However, both groups continued their old treatment (oral hypoglycemic or subcutaneous insulin).Results: On 12-month follow-up, in Group-1, palpitation improved in 16 of 17 (94.1%), giddiness improved in 12 of 20 (60.0%), constipation improved in 7 of 12 (58.3%), diarrhea improved in 7 of 8 (87.5%), erectile dysfunction improved in 3 of 5 (60.0%), abdominal fullness improved in 12 of 17 (70.5%), and abnormal sweating improved in 6 of 20 (30%). In comparison to this, in Group 2, palpitation improved in 6 of 19 (31.5%), giddiness improved in 2 of 15 (13.3%), constipation improved in 3 of 13 (23.0%), diarrhea improved in 3 of 7 (42.8%), erectile dysfunction improved in 3 of 5 (20.0%), abdominal fullness improved in 4 of 13 (13.7%), and abnormal sweating improved in 5 of 17 (29.4%).Conclusion: At the conclusion of our study, we found that patients, who were previously refractory to conventional pharmacotherapy, showed a considerable response to CIIIT with most patients giving a history of improvement in their symptoms after therapy and during follow-up. Therefore, it is recommended that patients presenting with complaints of diabetic autonomic neuropathy should be managed by CIIIT rather than the conventional pharmacological therapies.

Management of Leptomeningeal Metastases in Non-oncogene Addicted Non-small Cell Lung Cancer.

Brain metastases in non-small cell lung cancer (NSCLC) patients are more often detected due to imaging modalities improvements but also emerge because of improved treatments of the primary tumor which lead to a longer survival. In this context, development of leptomeningeal metastases (LM) is a devastating complication and its prognosis remains poor despite advances in systemic and local approaches. Histology characterization of NSCLC and molecular expression influence LM management. For those with “oncogene addiction,” new generation epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) were developed to strongly penetrate the blood-brain barrier (BBB) with the aim to prevent central nervous system cancer dissemination, eventually impacting on LM appearance and its subsequent management. Systemic chemotherapy, often combined with intrathecal chemotherapy (when possible), was one of common indications for lung cancer patients affected by LM, without driver mutations and a good performance status but currently, with the advent of innovative systemic approaches treatment solutions in this subgroup of patients are rapidly evolving. Whole brain radiation therapy (WBRT) is the conventional treatment for patients with brain metastases. Furthermore, modern radiation techniques, as stereotactic radiotherapy (SRT), improve outcomes in those cases with a limited number of lesions. However, LM represent a minority of CNS metastases and few literature data are available to drive the radiotherapy approach. Considering all relevant progress made in this setting, after a literature review, the aim of this paper is to discuss about recent developments and therapeutic options in LM management of non-oncogene addicted NSCLC.

Fractional CO2 laser contributes to the treatment of non-segmental vitiligo as an adjunct therapy: a systemic review and meta-analysis.

The treatment of stable non-segmental vitiligo is often challenging, which new therapies are being searched. Multiple clinical trials have proposed the benefits and safety of using fractional carbon dioxide (CO2) laser as an adjunct therapy to conventional treatments. This study aimed to evaluate the safety and efficacy of fractional carbon dioxide laser as a combination therapy to conventional treatments in patients with stable non-segmental vitiligo. A literature search using PubMed, EMBASE, and the Cochrane Library was performed for comparative studies among vitiligo patients treated with additional fractional CO2 laser. Clinical outcomes in the selected studies were compared, and a meta-analysis was performed via Review Manager version 5.3, according to the PRISMA guidelines. Six studies with a total of 184 patches/patients were included in the present meta-analysis. The combination therapy group had significantly superior results than that of the control group (≥ 75% re-pigmentation, risk ratio [RR] 2.80, 95% confidence interval [CI] 1.29-6.07; ≥ 50% re-pigmentation, RR 2.26, 95% CI 1.23-5.9; < 25% re-pigmentation, RR 0.57, 95% CI 0.43-0.75). Limitations of the study included the small number of studies and sample size, inadequate blinding of participants, and variation between therapy protocols. Meta-analysis revealed that using fractional CO2 laser in combination with conventional treatments is efficient and safe, and may be considered as an adjunct therapeutic option for patients with refractive non-segmental vitiligo.

A brief bedside visual art intervention decreases anxiety and improves pain and mood in patients with haematologic malignancies.

Treatment of cancer-related symptoms represents a major challenge for physicians. The purpose of this pilot study was to determine whether a brief bedside visual art intervention (BVAI) facilitated by art educators improves mood, reduces pain and anxiety in patients with haematological malignancies. Thirty-one patients (21 women and 10 men) were invited to participate in a BVAI where the goal of the session was to teach art technique for ~30min. Primary outcome measures included the change in visual analog scale, the State-Trait Anxiety Inventory and the Positive and Negative Affect Schedule scale, from baseline prior to and immediately post-BVAI. Total of 21 patients (19 women and two men) participated. A significant improvement in positive mood and pain scores (p=.003 and p=.017 respectively) as well as a decrease in negative mood and anxiety (p=.016 and p=.001 respectively) was observed. Patients perceived BVAI as overall positive (95%) and wished to participate in future art-based interventions (85%). This accessible experience, provided by artists within the community, may be considered as an adjunct to conventional treatments in patients with cancer-related mood symptoms and pain, and future studies with balanced gender participation may support the generalisability of these findings.

Locally advanced oral squamous cell carcinoma patients treated with photobiomodulation for prevention of oral mucositis: retrospective outcomes and safety analyses.

The well-established clinical efficacy of photobiomodulation (PBM) therapy in management of oral mucositis (OM) is leading to increasing use in oncology care. This protection and enhanced repair of damage to mucosal tissue have led to the question of the potential effects of PBM therapy on pre-malignant and malignant cells. The purpose of this study was to examine the outcome of cancer therapy and incidence of tumor recurrence in locally advanced oral squamous cell carcinoma (OSCC) patients treated with PBM therapy for OM. A retrospective clinical analysis of 152 advanced OSCC patients treated with prophylactic PBM therapy for radiotherapy-induced OM from January 2009 to December 2014 was conducted. Of the 152 OSCC patients treated with PBM therapy in this study, 19 (12.5%) had stage III and 133 (87.5%) had stage IV tumors. Of these, 52 (34.2%) received initial treatment with surgery followed by adjuvant radiotherapy, 94 (61.8%) with exclusive chemoradiation, and 6 (4%) with induction chemotherapy followed by surgery and radiotherapy. After a mean follow-up of 40.84 (± 11.71) months, the overall survival and disease-free survival rates were 46.7 and 51.8%, respectively. Forty-five (29.6%) patients developed local-regional recurrence, 10 (6.57%) patients developed distant relapse, and 19 (12.5%) developed new (second) primary tumors. Clinicopathological features and survival outcomes in the PBM-treated patients were similar to previously published data for conventional treatments in patients with advanced OSCC. In this study, prophylactic use of PBM therapy did not impact treatment outcomes of the primary cancer, recurrence or new primary tumors, or survival in advanced OSCC patients.

Why majority of heart failure with preserved ejection fraction randomized controlled trials fail? Part: I

Today, heart failure with preserved ejection fraction (HFpEF) remains one of the toughest Gordian knots in cardiovascular medicine with no visible effective and acceptable therapies. Owing to the complexity, urgency, and gravity of the problem of HFpEF, the present article has been divided into two parts – Part I deals with the description of the problem, and in Part II, the authors suggest innovative methodologies to deal with the problem globally. All the while we have been searching for a size which fits HFpEF, a less understood complex syndrome due to maladaptive changes in structural, functional, and biochemical aspects of the myocyte. Inflammation appears to be the underlying string which weaves together nitrosative/oxidative stress, endothelial dysfunction, downregulation of nitric oxide (NO) bioavailability/NO-mediated signaling, impaired myocardial bioenergetics, disturbed calcium handling, and concentric hypertrophy. Most of the HF with reduced EF (HFrEF) randomized controlled trials (RCTs) are positive, while the majority of HFpEF RCTs are either neutral, borderline, or negative leading to a huge vacuum in the therapeutic space of HFpEF. While few understand the statistical complexity of RCTs, many pretend to do so. Endeavor has been made in the present article to make the underlying concepts loud and lucid without going into statistical complexities. Attempts are being made to negotiate this problem by adopting/experimenting with innovative designs, enrichment trials, adaptive trials, umbrella trials, basket trials, and machine learning-based trials leading to what may be termed as “precision medicine, precision diagnosis, and precision therapy.” We have compared two recent negative HFpEF RCT's (TOPCAT trial - Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist, INDIE trial - Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF) with one positive HFrEF RCT (CASTLE AF trial - Catheter Ablation Versus Standard Conventional Treatment in Patients with Left Ventricular Dysfunction and Atrial Fibrillation), one negative HFrEF RCT (IRONOUT HF trial - Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure), one positive HFmEF / HFpEF randomized, parallel-group, blinded, multicenter trial (REDUCE LAP-HF TRIAL Phase 2: A Study to Evaluate the DC Devices, Inc. IASD™ System II to REDUCE Elevated Left Atrial Pressure in Patients with Heart Failure), one positive HFmEF / HFpEF non-randomized, multicenter, open label, single arm study (REDUCE LAP-HF TRIAL Phase 1: A Study to Evaluate the DC Devices, Inc. IASD™ System II to REDUCE Elevated Left Atrial Pressure in Patients with Heart Failure) in order to understand why majority of HFpEF Clinical Trials fail.

Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): a single-blind, randomised controlled trial

Conventional treatment of patients with adrenal insufficiency involves administration of glucocorticoids multiple times a day and has been associated with weight gain and metabolic impairment. The optimal glucocorticoid replacement therapy for these patients is highly debated because of the scarcity of evidence from randomised trials. We aimed to establish whether the timing and pharmacokinetics of glucocorticoid replacement therapy affect the metabolism and immune system of patients with adrenal insufficiency. We did a single-blind randomised controlled trial at two reference university hospitals in Italy. Eligible patients (aged 18-80 years) with adrenal insufficiency were on conventional glucocorticoid therapy and had been stable for at least 3 months before enrolment. Patients were randomly assigned (1:1) with a computer-generated random sequence stratified by type of adrenal insufficiency and BMI to continue conventional glucocorticoid therapy (standard treatment group) or to switch to an equivalent dose of once-daily, modified-release oral hydrocortisone (switch treatment group). Outcome assessors were masked to treatment allocation. The primary outcome was bodyweight change from baseline to 24 weeks. Secondary outcomes included immune cell profiles, susceptibility to infections, and quality of life. Efficacy analyses included all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT02277587. Between March 1, 2014, and June 30, 2016, 89 patients with adrenal insufficiency were randomly assigned to continue standard glucocorticoid therapy (n=43) or to switch to once-daily, modified-release hydrocortisone (n=46). At 24 weeks, bodyweight reduction was superior in patients in the once-daily hydrocortisone group compared with those in the standard treatment group (-2·1 kg [95% CI -4·0 to -0·3] vs 1·9 kg [-0·1 to 3·9]; treatment difference -4·0 kg, 95% CI -6·9 to -1·1; p=0·008). Additionally, patients in the once-daily hydrocortisone group had more normal immune cell profiles, reduced susceptibility to infections, and improved quality of life compared with the standard glucocorticoid therapy group. We observed no difference in frequency or severity of adverse events between the two intervention groups, although a lower cumulative number of recurrent upper respiratory tract infections was observed with once-daily hydrocortisone than with standard treatment (17 vs 38; p=0·016). Most adverse events were mild; three serious adverse events occurred in each group, of which one adverse advent (arthritis) in the switch treatment group could be considered drug related. Patients with adrenal insufficiency on conventional glucocorticoid replacement therapy multiple times a day exhibit a pro-inflammatory state and weakened immune defence. Restoration of a more physiological circadian glucocorticoid rhythm by switching to a once-daily, modified-release regimen reduces bodyweight, normalises the immune cell profile, reduces recurrent infections, and improves the quality of life of patients with adrenal insufficiency. Italian Ministry of University and Research.

A Chinese patent medicine Salvia miltiorrhiza depside salts for infusion combined with conventional treatment for patients with angina pectoris: A systematic review and meta-analysis of randomized controlled trials

Background: Currently, many trials have been conducted to investigate the beneficial and harmful effects of Salvia miltiorrhiza depside salts for infusion for treating patients with angina pectoris. It is important to systematically and criticallyevaluate the existing literature into providing a pooled effect to examine outcomes of angina pectoris with Salvia miltiorrhiza depside salts for infusion.Purpose: A systematic review and meta-analysis were performed to determine the clinical curative effect and safety of Salvia miltiorrhiza depside salts for infusion for angina pectoris and provide clear evidence to inform clinical practice.Method: The Cochrane Library, MEDLINE, EMBASE, and other four electronic Chinese databases were searched to identify relevant randomized controlled trials. Methodological quality and reporting quality of eligible studies was evaluated by using the Cochrane risk-of-bias tool and CONSORT for traditional Chinese medicine respectively. Meta-analysis was performed by RevMan 5.3 software.Result: Fifty-six randomized controlled trials involving 5503 patients were included. Most of the trials were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are improvements in angina symptoms, ECG improvement and reduction of nitroglycerin use. CHD mortality or rate of CHD events was not reported in any trial. Meta-analysis showed that Salvia miltiorrhiza depside salts for infusion combined with conventional treatment was better than conventional treatment alone in improving angina symptoms (RR= 1.28, 95% CI 1.24 to 1.31, p < 0.00001), the frequency of angina attack (time/week)(WMD=−1.47, 95% CI −2.16 to −0.78), reducing clinical symptom scores (WMD=−0.55, 95% CI −0.57 to −0.53, p < 0.000011), increasing physical limitation scores (WMD= 7.68, 95% CI 1.48 to 13.88, p = 0.02), improving ECG (RR= 1.32,95% CI 1.27 to 1.38, p < 0.00001) and reducing dosage of nitroglycerin (RR= 1.50, 95% CI: 1.26 to 1.77, p < 0.00001). In addition, Egger's regression tests was found there was publication bias (Kendall’ tau= 0.36, p < 0.01).Conclusion: The current systematic review indicates relevant evidence for Salvia miltiorrhiza depside salts for infusion combined with conventional treatments treating patient with angina pectoris. However, the results should be interpreted with caution due to the low methodological quality, the risk of publication bias, lack of important clinically relevant outcomes and inadequate reporting on adverse events of the included trials. International methodological and reporting standards could help researchers conduct well designed trials and generate better evidence for Salvia miltiorrhiza depside salts for infusion.

Role of N-acetylcysteine treatment in non-acetaminophen-induced acute liver failure: A prospective study.

Background/Aims:Acute liver failure (ALF) is a rare but severe medical emergency. To date, there is no established treatment for non-acetaminophen-induced acute liver failure (NAI-ALF) other than liver transplantation, and little is known about the use of N-acetylcysteine (NAC) in NAI-ALF. A randomized case control study was conducted with the aim to determine the effect of NAC on the mortality of NAI-ALF patients, as well as to evaluate the safety and efficacy of NAC use.Patients and Methods:A total of 80 patients diagnosed with NAI-ALF were included in the study. Forty patients received NAC infusion for 72 h whereas the control group received placebo. The variables evaluated were demographic characteristics, signs and symptoms, biochemical parameters, and clinical course during hospitalization.Results:The two groups (NAC and control) were comparable for various baseline characteristics (such as etiology of ALF, INR, alanine aminotransferase, creatinine, albumin, and grade of encephalopathy), except for age. Although majority of patients had undetermined etiology (32.5% in NAC group and 42.5% in control group), the second main cause was acute hepatitis E and drug or toxin-induced ALF. The mortality decreased to 28% with the use of NAC versus 53% in the control group (P = 0.023). The use of NAC was associated with shorter length of hospital stay in survived patients (P = 0.002). Moreover, the survival of patients was improved by NAC (P = 0.025). Also, drug-induced ALF showed improved outcome compared to other etiologies.Conclusion:The findings of the study recommend the use of NAC along with conventional treatments in patients with NAI-ALF in non-transplant centers while awaiting referrals and conclude the use of NAC as safe.

Clinical effectiveness of acupuncture on Parkinson disease: A PRISMA-compliant systematic review and meta-analysis.

Parkinson's disease (PD) is the second-most-common chronic and progressive neurodegenerative disease. The long-term use of levodopa leads to a loss of efficacy and to complications. Therefore, many patients with PD have turned to complementary therapies to help relieve their symptoms. Acupuncture is most commonly used as a complementary therapy in patients with PD. This paper presents a systematic review and meta-analysis of the effects of acupuncture for patients with PD. This study was performed to summarize and evaluate evidence regarding the effectiveness of acupuncture in the relief of PD symptoms. Seven databases, namely, MEDLINE, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure [CNKI], and three Korean medical databases, were searched from their inception through August 2015 without language restrictions. Randomized controlled trials (RCTs) were included if they contained reports of acupuncture compared with no treatment and conventional treatment alone or acupuncture plus conventional treatment compared with conventional treatment alone for PD symptoms. Assessments were performed with the unified PD rating scales (UPDRS) I, II, III, and IV and the total score, the Webster scale, and effectiveness rating. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale and the Cochrane risk of bias (ROB). In all, 982 potentially relevant articles were identified; 25 RCTs met our inclusion criterion, 19 of 25 RCTs were high-quality studies (i.e., a score of 6 or higher). The included RCTs showed favorable results for acupuncture plus conventional treatment compared with conventional treatment alone in the UPDRS II, III, and IV and the total score. Acupuncture was effective in relieving PD symptoms compared with no treatment and conventional treatment alone, and acupuncture plus conventional treatment had a more significant effect than conventional treatment alone. We performed a systematic review and meta-analysis to evaluate the use of acupuncture for relief of PD symptoms and found that acupuncture has significant positive effects. Acupuncture can be considered as a combination treatment with conventional treatment for patients with PD. Further studies on this topic should be carried out according to rigorous methodological designs in both the East and the West.

Health technology assessment of magnet therapy for relieving pain.

Background: Magnet therapy has been used increasingly as a new method to alleviate pain. Magnetic products are marketed with claims of effectiveness for reducing pain of various origins. However, there are inconsistent results from a limited number of randomized controlled trials (RCTs) testing the analgesic efficacy of magnet therapy. This study aimed to evaluate the safety and effectiveness of magnet therapy on reliving various types of pain. Methods: A systematic search of two main medical databases (Cochrane Library and Ovid Medline) was conducted from 1946 to May 2014. Only English systematic reviews that compared magnet therapy with other conventional treatments in patients with local pain in terms of pain relieving measures were included. The results of the included studies were thematically synthesized. Results: Eight studies were included. Magnet therapy could be used to alleviate pain of various origins including pain in various organs, arthritis, myofascial muscle pain, lower limb muscle cramps, carpal tunnel syndrome and pelvic pain. Results showed that the effectiveness of magnetic therapy was only approved in muscle pains, but its effectiveness in other indications and its application as a complementary treatment have not been established. Conclusion: According to the results, it seems that magnet therapy could not be an effective treatment for relieving different types of pain. Our results highlighted the need for further investigations to be done in order to support any recommendations about this technology.